臨床検査52巻11号

2008年10月発行

特集 ホルモンの病態異常と臨床検査 各論Ⅰ　ホルモンの病態異常と検査 9．血管制御因子

4) グレリン

著者： 細田洋司¹ 寒川賢治²

所属機関： ¹国立循環器病センター研究所生化学部 ²国立循環器病センター研究所

ページ範囲：P.1298 - P.1303

はじめに

　グレリン(ghrelin)は，1999年に筆者らによりG蛋白質共役型のオーファン受容体GHS(growth hormone secretagogue：成長ホルモン分泌促進因子)受容体の内因性リガンドとして，ヒトおよびラットの胃組織から同定されたGH分泌ホルモンである¹⁾．グレリンにはGH分泌促進作用のみならず，摂食調節やエネルギー代謝調節機能，循環器系に対する作用も認められ，またグレリンとエネルギー代謝調節に関連する疾患や病態生理とのかかわりも明らかになりつつある．

参考文献

1) Kojima M, Hosoda H, Date Y, et al：Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature　402：656-660, 1999

2) Hosoda H, Kojima M, Matsuo H, et al：Purification and characterization of rat des-Gln14-Ghrelin, a second endogenous ligand for the growth hormone secretagogue receptor. J Biol Chem　275：21995-22000, 2000

3) Hosoda H, Kojima M, Mizushima T, et al：Structural divergence of human ghrelin. Identification of multiple ghrelin-derived molecules produced by post-translational processing. J Biol Chem　278：64-70, 2003

4) Date Y, Kojima M, Hosoda H, et al：Ghrelin, a novel growth hormone-releasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans. Endocrinology　141：4255-4261, 2000

5) Hayashida T, Nakahara K, Mondal MS, et al：Ghrelin in neonatal rats：distribution in stomach and its possible role. J Endocrinol　173：239-245, 2002

6) Hosoda H, Kojima M, Matsuo H, et al：Ghrelin and des-acyl ghrelin：two major forms of rat ghrelin peptide in gastrointestinal tissue. Biochem Biophys Res Commun　279：909-913, 2000

7) Yang J, Brown MS, Liang G, et al：Identification of the acyltransferase that octanoylates ghrelin, an appetite-stimulating peptide hormone. Cell　132：387-396, 2008

8) Nakazato M, Murakami N, Date Y, et al：A role for ghrelin in the central regulation of feeding. Nature　409：194-198, 2001

9) Date Y, Murakami N, Toshinai K, et al：The role of the gastric afferent vagal nerve in ghrelin-induced feeding and growth hormone secretion in rats. Gastroenterology　123：1120-1128, 2002

10) Akamizu T, Murayama T, Teramukai S, et al：Plasma ghrelin levels in healthy elderly volunteers：the levels of acylated ghrelin in elderly females correlate positively with serum IGF-I levels and bowel movement frequency and negatively with systolic blood pressure. J Endocrinol　188：333-344, 2006

11) Hosoda H, Doi K, Nagaya N, et al：Optimum collection and storage conditions for ghrelin measurements：octanoyl modification of ghrelin is rapidly hydrolyzed to desacyl ghrelin in blood samples. Clin Chem　50：1077-1080, 2004

12) Hosoda H, Kangawa K：The autonomic nervous system regulates gastric ghrelin secretion in rats. Regul Pept　146：12-18, 2008

13) Nagaya N, Kojima M, Uematsu M, et al：Hemodynamic and hormonal effects of human ghrelin in healthy volunteers. Am J Physiol Regul Integr Comp Physiol　280：R1483-1487, 2001

14) Nagaya N, Uematsu M, Kojima M, et al：Chronic administration of ghrelin improves left ventricular dysfunction and attenuates development of cardiac cachexia in rats with heart failure. Circulation　104：1430-1435, 2001

15) Matsumura K, Tsuchihashi T, Fujii K, et al：Central ghrelin modulates sympathetic activity in conscious rabbits. Hypertension　40：694-699, 2002

16) Wiley KE, Davenport AP：Comparison of vasodilators in human internal mammary artery：ghrelin is a potent physiological antagonist of endothelin-1. Br J Pharmacol　136：1146-1152, 2002

17) Shinde UA, Desai KM, Yu C, et al：Nitric oxide synthase inhibition exaggerates the hypotensive response to ghrelin：role of calcium-activated potassium channels. J Hypertens　23：779-784, 2005

18) Nagaya N, Moriya J, Yasumura Y, et al：Effects of ghrelin administration on left ventricular function, exercise capacity, and muscle wasting in patients with chronic heart failure. Circulation　110：3674-3679, 2004